*Soo In Choi and Dawn Chung contributed equally to this study as first authors.
The aim of this study was to investigate the association between regional body fat distribution, especially leg fat mass, and the prevalence of diabetes mellitus (DM) in adult populations.
A total of 3,181 men and 3,827 postmenopausal women aged 50 years or older were analyzed based on Korea National Health and Nutrition Examination Surveys (2008 to 2010). Body compositions including muscle mass and regional fat mass were measured using dual-energy X-ray absorptiometry.
The odds ratios (ORs) for DM was higher with increasing truncal fat mass and arm fat mass, while it was lower with increasing leg fat mass. In a partial correlation analysis adjusted for age, leg fat mass was negatively associated with glycosylated hemoglobin in both sexes and fasting glucose in women. Leg fat mass was positively correlated with appendicular skeletal muscle mass and homeostasis model assessment of β cell. In addition, after adjusting for confounding factors, the OR for DM decreased gradually with increasing leg fat mass quartiles in both genders. When we subdivided the participants into four groups based on the median values of leg fat mass and leg muscle mass, higher leg fat mass significantly lowered the risk of DM even though they have smaller leg muscle mass in both genders (
The relationship between fat mass and the prevalence of DM is different according to regional body fat distribution. Higher leg fat mass was associated with a lower risk of DM in Korean populations. Maintaining leg fat mass may be important in preventing impaired glucose tolerance.
As the life span of individuals increases, metabolic disorder, especially type 2 diabetes mellitus (DM), has also been increasing rapidly worldwide [
Several recent studies have suggested that adipose tissue stored in various body locations differentially impact metabolic health. Hu et al. [
Sarcopenia, characterized by low muscle mass, has been considered to be associated with insulin resistance and type 2 diabetes [
Although adipose tissue deposited in different body locations may differentially impact glucose tolerance, few studies have examined the association between regional body fat distribution and the prevalence of DM. In addition, while some studies have already suggested that both higher leg fat mass and higher leg muscle mass have beneficial effects on metabolic health, there are no studies regarding which parameter—leg fat mass or muscle mass—may be more important for diabetes in adult populations. The aim of our study was to determine whether the association between fat mass and the prevalence of DM is influenced by site-specific adipose tissue accumulation in relatively healthy Korean adult populations. We also evaluated the relative contributions of leg fat mass and leg muscle mass to DM prevalence according to sex.
We recruited participants from the 2008 to 2010 Korea National Health and Nutrition Examination Surveys (KNHANES). The KNHANES has been performed periodically since 1998 by the Division of Chronic Disease Surveillance of the Korean Centers for Disease Control and Prevention in order to assess the health and nutritional status of the civilian, non-institutionalized population of Korea. It is a cross-sectional and nationally representative survey, composed of a health interview survey, a nutrition survey, and a health examination survey. Data were collected by household interviews and by direct, standardized physical examinations conducted in mobile examination centers. Daily total energy intake and medical history were evaluated using a 24-hour recall method. Regular exercise was indicated as “yes” if the subject exercised for more than 20 minutes at a time and more than three times per week. Women were also asked whether their menstruation had stopped and whether they had been treated with hormone replacement therapy. Postmenopausal status was defined as the self-reported cessation of menstruation for more than 1 year only and we excluded women who had undergone a hysterectomy (
Body weight and height were obtained using standard protocols. Waist circumference was measured at the narrowest point between the lower borders of the rib cage and the uppermost borders of the iliac crest at the end of normal expiration. Well-trained observers manually measured blood pressure with a mercury sphygmomanometer (Baumanometer; WA Baum Co., Copiague, NY, USA). Body composition, including truncal/peripheral fat mass and appendicular skeletal muscle mass (ASM), were measured by dual-energy X-ray absorptiometry (DXA; QDR 4500A; Hologic Inc., Waltham, MA, USA). Collected blood samples were immediately refrigerated, transported to the Central Testing Institute in Seoul, Korea, and analyzed within 24 hours. Fasting plasma glucose, total cholesterol, triglycerides (TG), and high density lipoprotein cholesterol (HDL-C) levels were measured with a Hitachi 700–110 chemistry analyzer (Hitachi, Tokyo, Japan). Glycosylated hemoglobin (HbA1c) levels were analyzed by high performance liquid chromatography using HLC-723G7 (Tosoh, Tokyo, Japan) in subjects with DM. Serum 25-hydroxyvitamin D3 level was measured by radioimmunoassay (DiaSorin Inc., Stillwater, MN, USA) using a γ-counter (1470 Wizard; PerkinElmer, Turku, Finland). The homeostasis model assessment of β-cell function (HOMA-β) was calculated using the following formula: [fasting plasma insulin (µIU/mL)×20]/[fasting glucose (mmol/L)–3.5] [
We defined DM as the presence of 1 or more of the following components: (1) fasting plasma glucose 126 mg/dL (7.0 mmol/L) or higher; (2) a medical diagnosis of DM by a trained medical professional; and (3) treatment with oral hypoglycemic agents or insulin injections.
Statistical analyses were conducted using PASW Statistics version 20 (IBM Co., Armonk, NY, USA). A comparison between the groups was performed using the
To investigate the independent contribution of trunk and extremities adiposity to DM, we calculated the adjusted OR of each kilogram increase in trunk and upper/lower extremities fat mass for DM using a multiple logistic regression analysis (
In a partial correlation analysis adjusted for age, leg fat mass was positively associated with BMI, trunk fat mass, and arm fat mass in both sexes (
When the participants were classified into four groups according to sex-specific leg fat mass quartiles, the OR for the presence of DM significantly decreased gradually as leg fat mass increased in both sexes after adjustment for potential confounding factors (
Our study found that higher leg fat mass was independently associated with a lower risk of DM in adult populations. We also demonstrated that adipose tissue, deposited in different body locations, may differentially impact the risk of DM. In addition, we observed that subjects with higher leg fat mass have a lower risk of DM even though they have a low leg muscle mass; but subjects with lower leg fat mass have a higher risk of DM even though they have large leg muscle mass. To our knowledge, this is the first population-based study of the association between body compositions and DM considering body fat distribution.
Adiposity is a well-known risk factor for DM and cardiovascular disease [
In our study, in contrast to trunk fat mass and arm fat mass, there was a negative association between leg fat mass and DM prevalence. This result is consistent with a recent study showing that leg fat mass was inversely associated with glucose levels and homeostatic model assessment of insulin resistance from an oral glucose tolerance test [
Recently, the interaction between appendicular muscle mass and glucose tolerance has been a subject of interest. Because skeletal muscle is responsible for insulin-mediated glucose disposal, low muscle mass can have a negative impact on glucose tolerance. Therefore, previous studies have shown that larger hip or thigh circumference is associated with decreased diabetes risk [
In addition, although in both genders there was a significant inverse relationship between leg fat mass and DM after adjustment for confounding factors, including BMI, we found that the association between leg fat mass and DM was more prominent in postmenopausal women than in men based on an independent
The major strength of our study is that we analyzed representative data collected from a nationwide survey in Korea, including large numbers of participants of both sexes. In addition, we compared significant associations between body compositions and DM according to gender for the first time. However, there were some limitations in this study. First, as the present study was a cross-sectional study, a causal relationship between leg fat mass and diabetes could not be definitively established. Second, because DXA is unable to distinguish between subcutaneous and intramuscular fat in the lower and upper extremities, we could not conclude whether the beneficial effects of leg fat on glucose tolerance were due to subcutaneous or intramuscular fat. Third, although the association between leg fat and glucose tolerance was presumed to result from adipokines and inflammatory factors, we could not further prove it due to lack of data. Finally, as we did not examine the associations between other ethnic groups with different body compositions, we were not able to extend our results to other ethnic groups.
In conclusion, our study demonstrates that, in contrast to trunk and arm adiposity, there is a favorable association of leg adiposity with DM in Korean adults aged 50 years or older. We also found that the contributory effects of lower extremity fat on DM are more dominant than those of the lower extremity muscle. Our findings support the notion that subcutaneous fat and glucose metabolism are intimately interlinked. Further prospective studies are needed to confirm the causal interactions between leg fat mass and the development of diabetes.
No potential conflict of interest relevant to this article was reported.
Characteristic | Men | Women | ||||
---|---|---|---|---|---|---|
Non-DM ( |
DM ( |
Non-DM ( |
DM ( |
|||
Age, yr | 63.24±8.85 | 64.29±8.38 | 0.011 | 63.68±8.88 | 67.04±7.97 | <0.001 |
Weight, kg | 65.08±9.60 | 67.84±9.66 | <0.001 | 56.06±8.56 | 58.91±9.07 | <0.001 |
BMI, kg/m2 | 23.44±2.91 | 24.43±2.90 | <0.001 | 23.92±3.16 | 25.24±3.36 | <0.001 |
Waist circumference, cm | 84.38±8.50 | 88.32±8.67 | <0.001 | 81.49±9.15 | 87.04±9.23 | <0.001 |
Current smoking | 847 (33.8) | 164 (32.0) | 0.424 | 140 (4.6) | 16 (23.4) | 0.272 |
Regular exercise | 471 (18.8) | 83 (16.2) | 0.169 | 392 (12.8) | 43 (9.2) | 0.031 |
SBP, mm Hg | 124.13±17.16 | 125.67±16.33 | 0.061 | 125.53±17.87 | 131.44±18.24 | <0.001 |
DBP, mm Hg | 77.03±10.45 | 75.35±10.26 | <0.001 | 76.43±10.05 | 75.70±10.15 | 0.144 |
Fasting glucose, mmol/L | 5.4±0.6 | 8.1±2.6 | <0.001 | 5.84±1.54 | 5.84±1.28 | <0.001 |
HOMA-β | 104.24±52.73 | 61.42±55.92 | <0.001 | 117.37±53.01 | 75.72±66.83 | <0.001 |
Total cholesterol, mmol/L | 4.85±0.92 | 4.69±0.99 | 0.025 | 5.28±0.91 | 5.17±1.01 | 0.025 |
LDL-C, mmol/L | 2.80±0.89 | 2.57±0.96 | <0.001 | 3.22±0.83 | 3.05±0.91 | <0.001 |
HDL-C, mmol/L | 1.18±0.29 | 1.08±0.26 | <0.001 | 1.25±0.28 | 1.16±0.27 | <0.001 |
Triglyceride, mmol/L | 3.68±2.23 | 4.25±2.40 | <0.001 | 3.46±1.95 | 4.17±2.26 | <0.001 |
Total body fat, % | 21.98±5.23 | 23.44±4.91 | <0.001 | 33.85±5.59 | 34.85±5.05 | <0.001 |
Truncal fat mass, kg | 8.06±3.12 | 9.29±2.99 | <0.001 | 10.15±3.28 | 11.73±3.35 | <0.001 |
Arm fat mass, kg | 1.50±0.52 | 1.65±0.51 | <0.001 | 2.32±0.73 | 2.55±0.78 | <0.001 |
Leg fat mass, kg | 3.89±1.31 | 3.98±1.29 | 0.141 | 5.77±1.68 | 5.44±1.70 | <0.001 |
ASM/weight, % | 31.77±2.71 | 30.49±2.49 | 0.036 | 25.02±2.65 | 24.17±2.46 | <0.001 |
Leg muscle mass, kg | 15.26±2.23 | 15.33±2.38 | 0.510 | 10.62±1.56 | 10.76±1.62 | 0.090 |
Glucose lowering drug use | ||||||
No medication | - | 124 (24.2) | - | - | 52 (10.1) | - |
Insulin | - | 34 (6.6) | - | - | 40 (8.5) | - |
Oral anti-hypoglycemic agent | - | 355 (69.2) | - | - | 377 (80.4) | - |
Current smoking | 847 (338) | 164 (32.0) | 0.424 | 140 (4.6) | 16 (3.4) | 0.273 |
Regular exercise | 471 (18.8) | 83 (16.2) | 0.169 | 393 (12.8) | 43 9 (9.25) | 0.030 |
Total energy intake, kcal | 2,022.1±792.9 | 2,112.1±772.1 | 0.023 | 1,480.5±698.2 | 1,563.1±593.5 | 0.008 |
Hormone replacement (women) | - | - | - | 478 (16.3) | 53 (12%) | 0.019 |
Values are presented as mean±standard deviation or number (%).
DM, diabetes mellitus; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; HOMA-β, homeostasis model assessment β-cell; LDL-C, low density lipoprotein cholesterol; HDL-C, high density lipoprotein cholesterol; ASM, appendicular skeletal mass.
Variable | Leg fat mass, kg | |
---|---|---|
Men | Women | |
Body composition | ||
BMI, kg/m2 | 0.66a | 0.72a |
Truncal fat mass, kg | 0.83a | 0.68a |
Arm fat mass, kg | 0.85a | 0.78a |
Appendicular skeletal muscle, kg | 0.33a | 0.35a |
Leg muscle mass, kg | 0.36a | 0.37a |
Metabolic parameter | ||
HbA1c, % | −0.10b | −0.14c |
Fasting glucose, mg/dL | −0.07 | −0.09b |
Total cholesterol, mg/dL | 0.09b | 0.01 |
HDL-C, mg/dL | −0.15c | 0.01 |
Triglyceride, mg/dL | 0.11b | −0.01 |
HOMA-β | 0.22a | 0.13a |
Values are partial correlation coefficients between variables and leg fat mass adjusted for age.
BMI, body mass index; HbA1c, glycosylated hemoglobin; HDL-C, high density lipoprotein cholesterol; HOMA-β, homeostasis model assessment β-cell.
a
Sex | Leg fat mass | ||||
---|---|---|---|---|---|
Quartile 1 | Quartile 2 | Quartile 3 | Quartile 4 | ||
Mena | Reference | 0.45 (0.34–0.61) | 0.36 (0.26–0.49) | 0.16 (0.11–0.25) | <0.001 |
Womenb | Reference | 0.44 (0.32–0.59) | 0.35 (0.25–0.49) | 0.16 (0.11–0.25) | <0.001 |
Quartile 1: ≤2.97 kg in men and ≤4.54 kg in women; Quartile 2: 2.98 to 3.81 kg in men and 4.55 to 5.57 kg in women; Quartile 3: 3.82 to 4.66 kg in men and 5.58 to 6.71 kg in women; Quartile 4: ≥4.67 kg in men and ≥6.72 kg in women.
aData adjusted for age, body mass index, leg muscle mass, current smoking status, regular exercise, total cholesterol, triglyceride, systolic blood pressure, and daily total energy intake, bData adjusted for age, body mass index, leg muscle mass, current smoking status, regular exercise, total cholesterol, triglyceride, systolic blood pressure, daily total energy intake, and hormone replacement therapy status.
Sex | Body composition group | ||||
---|---|---|---|---|---|
LF-LM | LF-HM | HF-LM | HF-HM | ||
Mena | Reference | 1.31 (0.88–1.96) | 0.69 (0.49–0.96) | 0.60 (0.39–0.90) | <0.001 |
Womenb | Reference | 1.38 (1.02–1.87) | 0.47 (0.32–0.69) | 0.57 (0.40–0.81) | <0.001 |
We subdivided men and women in each age group into four groups according to leg fat mass and leg muscle mass, which were halved into low or high values by the median value.
LF-LM, low fat-low muscle group; LF-HM, low fat-high muscle group; HF-LM, high fat-low muscle group; HF-HM, high fat-high muscle group.
aData adjusted for age, body mass index, current smoking status, regular exercise, total cholesterol, triglyceride, systolic blood pressure, and daily total energy intake, bData adjusted for age, body mass index, current smoking status, regular exercise, total cholesterol, triglyceride, systolic blood pressure, daily total energy intake, and hormone replacement therapy status.